A chemoenzymatic total synthesis of 13-deoxytetrodecamycin – Identification and application of TedJ, a new Diels-Alderase, in the synthesis of an antibiotic Joe Russell 1 , Chris Perry 1 , Catherine R. Back 2 , Paul R. Race 2 , Christine L Willis 1 and Nick Lees 1 1 School of Chemistry, University of Bristol, UK, 2 School of Biochemistry, University of Bristol, UK The Diels-Alderase TedJ has been identified in the biosynthetic pathway towards antibiotic 13-deoxytetrodecamycin in Streptomyces WAC04657. TedJ has been expressed and shown to enantioselectively catalyse trans -decalin formation of the protected natural substrate, a reaction unattainable by chemical means.
A route to 13-deoxytetrodecamycin from the TedJ cyclisation product has been developed to afford a racemic total synthesis of the antibiotic, with a chemoenzymatic total synthesis swiftly following, confirming the proposed structure of 13-deoxytetrodecamycin. The antibiotic properties of 13-deoxytetrodecamycin are being tested alongside derivitisation work, with the substrate specificity of TedJ likewise continuing to be probed. References 1. Gverzdys and J. R. Nodwell, J. Bacteriol. , 2016, 198 , 1965–1973. 2. T. Gverzdys, G. Kramer and J. R. Nodwell, Bioorganic Med. Chem. , 2016, 24 , 6269–6275. 3. T. Gverzdys, M. K. Hart, S. Pimentel-Elardo, G. Tranmer and J. R. Nodwell, J. Antibiot. (Tokyo). , 2015, 68 , 698–702. 4. Z. Tian, P. Sun, Y. Yan, Z. Wu, Q. Zheng, S. Zhou, H. Zhang, F. Yu, X. Jia, D. Chen, A. Mándi, T. Kurtán and W. Liu, Nat. Chem. Biol. , 2015, 11 , 259–265.
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